DESCRIPTION: (Adapted from the abstract on page 2 of the application) In an effort to determine how long present treatments must be continued to permit elimination of the long-lived viral DNA reservoir (if possible) and to provide a basis for the development of new therapeutic strategies, the nature of this reservoir must be characterized. This project will study the decay rate of this reservoir and the applicability of existing paradigms of pre- and post-integration viral latency through three aims: (1) Infectivity assays and serial quantitative assays for both integrated and unintegrated HIV DNA will be used to determine whether infectivity associated with latently infected cells in the setting of undetectable (<50 copies/ml) plasma viremia reflects pre- or post-integration latency and whether the exhaustion of this reservoir is feasible with current therapies. (2) HIV pol sequences of sequential HIV isolates from treatment suppressed patients, will be studied to monitor for the development of drug resistance and sequence evolution which would indicate that this population of cells is being replenished by ongoing viral replication and thus be associated with a risk for treatment failure. (3) The application of sensitive quantitative assays for spliced HIV transcripts will be used to determine whether, some or all latently infected cells remain transcriptionally active thereby producing one or more gene products that can be targeted by the host immune response.